KSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma

Kaposi's sarcoma-associated herpesvirus (KSHV) vGPCR is a constitutively active G protein-coupled receptor that subverts proliferative and inflammatory signaling pathways to induce cell transformation in Kaposi's sarcoma. Cyclooxygenase-2 (COX-2) is an inflammatory mediator that plays a key regulatory role in the activation of tumor angiogenesis. Hereby we demonstrate, using two different transformed mouse models, and tumorigenic full KSHV genome-bearing cells, including KSHV-Bac16 based mutant system with a vGPCR deletion, that vGPCR upregulates COX-2 expression and activity, signaling through selective MAPK cascades. We show that vGPCR expression triggers signaling pathways that upregulate COX-2 levels due to a dual effect upon both its gene promoter region and, in mature mRNA, the 3'UTR region that control mRNA stability. Both events are mediated by signaling through ERK1/2 MAPK pathway. Inhibition of COX-2 in vGPCR-transformed cells impairs vGPCRdriven angiogenesis and treatment with the COX-2-selective inhibitory drug Celecoxib produces a significant decrease in tumor growth, pointing to COX-2 activity as critical for vGPCR oncogenicity in vivo and indicating that COX-2-mediated angiogenesis could play a role in KS tumorigenesis. These results, along with the overexpression of COX-2 in KS lesions, define COX-2 as a potential target for the prevention and treatment of KSHV-oncogenesis.Fil: Medina, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: D´Agostino, Agata. University Of Miami Miller School Of Medicine; Estados UnidosFil: Ma, Qi. University Of Miami Miller School Of Medicine; Estados UnidosFil: Eroles, Pilar. University Of Miami Miller School Of Medicine; Estados UnidosFil: Cavallin, Lucas. University Of Miami Miller School Of Medicine; Estados UnidosFil: Chiozzini, Chiara. Miller School Of Medicine; Estados UnidosFil: Sapochnik, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Hyjek, Elizabeth. University of Chicago; Estados UnidosFil: Cesarman, Ethel. Cornell University; Estados UnidosFil: Naipauer, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Mesri, Enrique Alfredo. University Of Miami Miller School Of Medicine; Estados UnidosFil: Coso, Omar Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Voce: Prelievi e analisi di campioni

Con la legge 30.6.2009 n. 85 l'Italia ha ratificato l'adesione al Trattato di Pr\ufcm, in vista del rafforzamento della cooperazione tra Stati nella lotta al terrorismo, alla criminalit\ue0 transfrontaliera e alla migrazione illegale, tramite lo scambio di informazioni genetiche. La novit\ue0 pi\uf9 saliente che l'adesione al Trattato ha importato nell'ordinamento interno concerne l'introduzione di un'inedita disciplina dei prelievi coattivi di materiale biologico, volta alla tutela dei diritti individuali nell'impiego processuale di strumenti tecnico-scientifici che consentano di non disperdere il materiale probatorio relativo ad un fatto criminoso. Il tema rievoca la tradizionale distinzione che attribuisce all'imputato la duplice funzione di \u201corgano\u201d ed \u201coggetto\u201d nella formazione della prova, a seconda del contributo attivo o passivo che lo stesso apporti alla vicenda processuale. Questi \ue8 considerato \u201corgano\u201d di prova nell'espletamento di attivit\ue0 che costituiscono esercizio del diritto di difesa, nelle due componenti, positiva e negativa, del diritto di difendersi provando e del diritto al silenzio. Viceversa, si parla di imputato come \u201coggetto\u201d di prova allorquando gli sia richiesto un mero pati rispetto all'attivit\ue0 di istruzione probatoria, come accade nelle ispezioni, nelle perquisizioni, nelle ricognizioni personali, nonch\ue9, pi\uf9 in generale, negli accertamenti che si espletano sul corpo del giudicabile, il quale viene in rilievo non come parte processuale, ma come mera entit\ue0 fisica. Il regime di nuovo conio \ue8 intervenuto a colmare la lacuna normativa lasciata dalla sentenza n. 238 del 1996 con cui la Corte costituzionale aveva dichiarato l'illegittimit\ue0 dell'art. 224, comma 2, c.p.p. nella parte in cui consentiva interventi peritali sul corpo della persona, in violazione del principio di riserva di legge che presidia, ex art. 13 Cost., la libert\ue0 personale. La pronuncia ha individuato un \u201cnocciolo duro\u201d rappresentato dalla libert\ue0 corporale, indissolubilmente legata ai principi di libert\ue0 morale, integrit\ue0 psico-fisica e salute della persona, non comprimibili a fini processuali. La Carta fondamentale prevede un'unica ipotesi di lesione del diritto alla salute nell'ambito dei trattamenti sanitari obbligatori, per finalit\ue0 estranee all'accertamento penale; la libert\ue0 morale, peraltro, rappresenta il quid pluris che sopravvive alla compressione del potere statale, persino durante la pi\uf9 intensa restrizione della libert\ue0 personale. Se questo \ue8 il quadro costituzionale di riferimento, \ue8 evidente come il previgente regime in materia di prelievi biologici coattivi abbia disatteso le indicazioni provenienti dalla Consulta. Difatti, a distanza di quasi un decennio dal monito del Giudice delle leggi, il legislatore intervenne (con la legge 31 luglio 2005, n. 155) \uabin un modo persino pi\uf9 imbarazzante dell'inerzia sino ad allora mantenuta\ubb, attribuendo un potere di intrusione corporale (attraverso il prelievo di capelli o saliva nel corso delle indagini) alla polizia giudiziaria, previa autorizzazione - anche orale, purch\ue9 confermata per iscritto - del pubblico ministero, a soli fini identificativi e purch\ue9 sussistesse il pericolo di alterazione o dispersione della res. Non era contemplato il potere giudiziale di disporre un prelievo biologico a fini peritali e l\u2019esclusivo orientamento teleologico dell\u2019atto d\u2019indagine ne limitava fortemente l\u2019utilit\ue0. Veniva, pertanto, inopinatamente elusa la doppia riserva, di legge e di giurisdizione, che presidia la materia. La riforma realizza una netta soluzione di continuit\ue0 rispetto alla normativa precedente, attraverso l'individuazione nell'organo giurisdizionale del baricentro del micro-sistema normativo dedicato ai prelievi biologici coattivi. Se la libert\ue0 personale pu\uf2 subire restrizioni per atto motivato dell'autorit\ue0 giudiziaria, pertanto anche del pubblico ministero, l'intrusione nella sfera corporale esige l'egida di un soggetto super partes, indifferente rispetto all'esito del processo. Il legislatore ha costruito una disciplina minuziosa, concernente sia l'an che il quomodo dei prelievi, in ossequio alla riserva di legge dettagliata (nei \u201cmodi\u201d e nei \u201ccasi\u201d) imposta dalla Consulta. Ne \ue8 derivato un apparato \uabmulti-livello\ubb, calibrato sulla sistematica del codice e diversificato in base all'orientamento teleologico dell'accertamento \u2013istituzionale, probatorio, investigativo o identificativo-, in cui ogni tipologia \ue8 rigidamente separata dalle altre

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press

Transverse momentum and pseudorapidity distributions of charged hadrons in pp collisions at (s)\sqrt(s) = 0.9 and 2.36 TeV

Measurements of inclusive charged-hadron transverse-momentum and pseudorapidity distributions are presented for proton-proton collisions at sqrt(s) = 0.9 and 2.36 TeV. The data were collected with the CMS detector during the LHC commissioning in December 2009. For non-single-diffractive interactions, the average charged-hadron transverse momentum is measured to be 0.46 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 0.9 TeV and 0.50 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 2.36 TeV, for pseudorapidities between -2.4 and +2.4. At these energies, the measured pseudorapidity densities in the central region, dN(charged)/d(eta) for |eta| < 0.5, are 3.48 +/- 0.02 (stat.) +/- 0.13 (syst.) and 4.47 +/- 0.04 (stat.) +/- 0.16 (syst.), respectively. The results at 0.9 TeV are in agreement with previous measurements and confirm the expectation of near equal hadron production in p-pbar and pp collisions. The results at 2.36 TeV represent the highest-energy measurements at a particle collider to date

Measurement of the charge ratio of atmospheric muons with the CMS detector

We present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/ c to 1 TeV/ c . The surface flux ratio is measured to be 1.2766±0.0032(stat.)±0.0032(syst.) , independent of the muon momentum, below 100 GeV/ c . This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experiments.We present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/c to 1 TeV/c. The surface flux ratio is measured to be 1.2766 \pm 0.0032(stat.) \pm 0.0032 (syst.), independent of the muon momentum, below 100 GeV/c. This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experiments

Transverse-momentum and pseudorapidity distributions of charged hadrons in pppp collisions at s\sqrt{s} = 7 TeV

Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at $\sqrt{s} = 7$~TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit-pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity \dnchdeta|_{|\eta| < 0.5} = 5.78\pm 0.01\stat\pm 0.23\syst for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from $\sqrt{s} = 0.9$ to 7~TeV is 66.1\%\pm 1.0\%\stat\pm 4.2\%\syst. The mean transverse momentum is measured to be 0.545\pm 0.005\stat\pm 0.015\syst\GeVc. The results are compared with similar measurements at lower energies.Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at sqrt(s) = 7 TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit-pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity, dN(charged)/d(eta), for |eta| < 0.5, of 5.78 +/- 0.01 (stat) +/- 0.23 (syst) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from sqrt(s) = 0.9 to 7 TeV is 66.1% +/- 1.0% (stat) +/- 4.2% (syst). The mean transverse momentum is measured to be 0.545 +/- 0.005 (stat) +/- 0.015 (syst) GeV/c. The results are compared with similar measurements at lower energies